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    Study Habits

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    This document discusses the process of regeneration and healing. It begins by defining regeneration as the growth of cells to replace lost tissue, while healing is the body's reparative response to wounds, inflammation or necrosis, often resulting in fibrosis. The key stages of healing are inflammation, proliferation of connective tissue cells, angiogenesis, collagen deposition, tissue remodeling and wound contraction. Growth factors and the extracellular matrix play important roles in regulating and guiding the healing process.

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    Study Habits

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    Modoro
    58 views51 pages
    This document discusses the process of regeneration and healing. It begins by defining regeneration as the growth of cells to replace lost tissue, while healing is the body's reparative response to wounds, inflammation or necrosis, often resulting in fibrosis. The key stages of healing are inflammation, proliferation of connective tissue cells, angiogenesis, collagen deposition, tissue remodeling and wound contraction. Growth factors and the extracellular matrix play important roles in regulating and guiding the healing process.

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    This document discusses the process of regeneration and healing. It begins by defining regeneration as the growth of cells to replace lost tissue, while healing is the body's reparative response to wounds, inflammation or necrosis, often resulting in fibrosis. The key stages of healing are inflammation, proliferation of connective tissue cells, angiogenesis, collagen deposition, tissue remodeling and wound contraction. Growth factors and the extracellular matrix play important roles in regulating and guiding the healing process.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    58 views51 pages

    Study Habits

    Uploaded by

    Modoro
    This document discusses the process of regeneration and healing. It begins by defining regeneration as the growth of cells to replace lost tissue, while healing is the body's reparative response to wounds, inflammation or necrosis, often resulting in fibrosis. The key stages of healing are inflammation, proliferation of connective tissue cells, angiogenesis, collagen deposition, tissue remodeling and wound contraction. Growth factors and the extracellular matrix play important roles in regulating and guiding the healing process.

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    of 51

    REGENERATION

    HEALING
    (repair)
    LEARNING OBJECTIVES
    • Review the normal physiology and concepts
    of cell proliferation, cell growth, cell “cycle”,
    and cell differentiation
    • Understand the basic factors of tissue
    regeneration
    • Understand the relationships between cells
    and their ExtraCellular Matrix (ECM)
    • Understand the roles of the major players of
    healing---angiogenesis, growth factors (GFs),
    and fibrosis
    • Differentiate 1st & 2nd intention healing
    DEFINITIONS:
    • REGENERATION: Growth of
    cells to replace lost tissues

    • HEALING: A reparative tissue


    response to a wound, inflammation or necrosis,
    often leads to fibrosis
    • GRANULATION TISSUE
    • “ORGANIZING” INFLAMATION
    REGENERATION
    • Replacement of lost structures
    • Is dependent on the type of
    normal turnover the original
    tissue has
    • Can be differentiated from
    “compensatory” growth
    HEALING (repair)
    • Needs a wound, inflammatory process, or
    necrosis
    • Many disease appearances anatomically are
    the result of “healing” such as
    atherosclerosis
    • Often ends with a scar
    • Fibrosis, as one of the 3 possible outcomes
    of inflammation, follows “healing”
    • Requires a connective tissue “scaffold”
    • Fibrosis occurs in proportion to the damage
    of the ECM
    Cell Population Fates
    • PROLIFERATION
    – Hormonal, especially steroid hormones
    – eg., EPO, CSF

    • DIFFERENTIATION *
    – UNIDIRECTIONAL, GAIN and LOSS
    • APOPTOSIS

    *One of the most KEY concepts in neoplasia


    ECTODERM
    MESODERM
    ENTODERM
    CELL CYCLE
    • G0
    – Quiescent (not a very long or dominent phase)
    • G1
    – PRE-synthetic, but cell GROWTH taking place
    • S
    – Cells which have continuous “turnover” have
    longer, or larger S-phases, i.e., DNA synthesis
    – S-phase of TUMOR CELLS can be prognostic
    • G2
    – PRE-mitotic
    • M (Mitotic:, P,M,A,T, Cytokinesis)
    CELL TYPES
    • Labile: eg., marrow, GI
    • Quiescent: liver, kidney
    • NON-mitotic: neuron,
    striated muscle
    STEM CELLS
    (TOTIPOTENTIAL*)

    • EMBRYONIC
    • ADULT
    EMBRYONIC
    STEM CELLS
    • DIFFERENTIATION

    • KNOCKOUT MICE ( mice raised


    with specific gene defects)

    • REPOPULATION OF DAMAGED
    TISSUES, in research
    ADULT
    STEM CELLS
    • MARROW
    (HEMOCYTOBLAST)
    (hematopoetic stem cells)

    • NON-MARROW
    (RESERVE)
    MARROW STROMAL CELL
    ADULT TISSUE DIFFERENTIATION and
    REGENERATION PARALLELS EMBRYONIC
    DEVELOPMENT
    Growth Factors (GFs)
    • Polypeptides
    • Cytokines
    • LOCOMOTION
    • CONTRACTILITY
    • DIFFERENTIATION
    • ANGIOGENESIS
    Growth Factors (GFs)
    • Epidermal
    • Transforming (alpha, beta)
    • Hepatocyte
    • Vascular Endothelial
    • Platelet Derived
    • Fibroblast
    • Keratinocyte
    • Cytokines (TNF, IL-1, Interferons)
    CELL PLAYERS
    (source AND targets)
    • Lymphocytes, especially T-cells
    • Macrophages
    • Platelets
    • Endothelial cells
    • Fibroblasts
    • Keratinocytes
    • “Mesenchymal” cells
    • Smooth muscle cells
    E(Epidermal) GF
    • Made in platelets, macrophages
    • Present in saliva, milk, urine, plasma
    • Acts on keratinocytes to migrate, divide
    • Acts on fibroblasts to produce
    “granulation” tissue
    T(Transforming) GF-alpha
    • Made in macrophages, T-cells,
    keratinocytes
    • Similar to EGF, also effect on
    hepatocytes
    H(Hepatocyte) GF
    • Made in “mesenchymal” cells
    • Proliferation of epithelium,
    endothelium, hepatocytes
    • Effect on cell “motility”
    VE(Vascular Endothelial) GF
    • Made in mesenchymal cells
    • Triggered by HYPOXIA
    • Increases vascular permeability
    • Mitogenic for endothelial cells
    • KEY substance in promoting
    “granulation” tissue
    PD(Platelet Derived) GF
    • Made in platelets, but also MANY
    other cell types
    • Chemotactic for MANY cells
    • Mitogen for fibroblasts
    • Angiogenesis
    • Another KEY player in granulation
    tissue
    F(Fibroblast) GF
    • Made in MANY cells
    • Chemotactic and mitogenic, for
    fibroblasts and keratinocytes
    • Re-epithelialization
    • Angiogenesis, wound contraction
    • Hematopoesis
    • Cardiac/Skeletal (striated) muscle
    T(Transforming) GF-beta
    • Made in MANY CELLS
    • Chemotactic for PMNs and MANY
    other types of cells
    • Inhibits epithelial cells
    • Fibrogenic
    • Anti-Inflammatory
    K(Keratinocyte) GF
    • Made in fibroblasts
    • Stimulates
    keratinocytes:
    – Migration
    – Proliferation
    – Differentiation
    I(Insulin-like) GF-1
    • Made in macrophages, fibroblasts
    • Stimulates:
    – Sulfated proteoglycans
    – Collagen
    – Keratinocyte migration
    – Fibroblast proliferation
    • Action similar to GH (Pituitary
    Growth Hormone)
    TNF (Tumor Necrosis Factor)
    • Made in macrophages, mast
    cells, T-cells
    • Activates macrophages
    • KEY influence on other
    cytokines
    Interleukins
    • Made in macrophages, mast cells,
    T-cells, but also MANY other cells
    • MANY functions:
    – Chemotaxis
    – Angiogenesis
    – REGULATION of other cytokines
    INTERFERONS
    • Made by lymphocytes,
    fibroblasts
    • Activates MACROPHAGES
    • Inhibits FIBROBLASTS
    • REGULATES other cytokines
    SIGNALING
    • Autocrine (same cell)

    • Paracrine (next door neighbor)


    (many GFs)

    • Endocrine (far away, delivered


    by blood, steroid hormones)
    TRANSCRIPTION FACTORS
    HEPATIC
    REGENERATION

    TNF
    IL6
    HGF
    ExtraCellular Matrix (ECM)
    • Collagen(s) I-XVIII
    • Elastin
    • Fibrillin
    • CAMs (Cell Adhesion Molecules)
    – Immunoglobulins, cadherins, integrins,
    selectins
    • Proteoglycans
    • Hyaluronic Acid
    ECM
    • Maintain cell differentiation
    • “Scaffolding”
    • Establish microenvironment
    • Storage of GF’s
    Collagen One - bONE (main component of bone)

    Collagen Two - carTWOlage (main component of cartilage)

    Collagen Three - reTHREEculate (main component of reticular fibers)

    Collagen Four - FLOOR - forms the basement membrane


    GENETIC COLLAGEN DISORDERS
    • I OSTEOGENESIS IMPERFECTA, E-D
    • II ACHONDROGENESIS TYPE II
    • III VASCULAR EHLERS-DANLOS
    • V CLASSICAL E-D
    • IX STICKLER SYNDROME
    • IV ALPORT SYNDROME
    • VI BETHLEM MYOPATHY
    • VII DYSTROPHIC EPIDERMOLYSIS BULLOS.
    • IX EPIPHYSEAL DYSPLASIAS
    • XVII GEN. EPIDERMOLYSYS BULLOSA
    • XV, XVIII KNOBLOCH SYNDROME
    DEFINITIONS:
    • REGENERATION:
    Growth of cells to replace lost tissues

    • HEALING: A reparative tissue


    response to a wound, inflammation or
    necrosis
    HEALING
    • FOLLOWS INFLAMMATION
    • PROLIFERATION and MIGRATION of
    connective tissue cells
    • ANGIOGENESIS (Neovascularization)
    • Collagen, other ECM protein synthesis
    • Tissue Remodeling
    • Wound contraction
    • Increase in wound strength (scar = fibrosis)
    ANGIOGENESIS
    (NEOVASCULARIZATION)
    • From endothelial precursor cells
    • From PRE-existing vessels
    • Stimulated/Regulated by GF’s,
    especially VEGF
    • Also regulated by ECM proteins
    • aka, “GRANULATION”, “GRANULATION
    TISSUE”, “ORGANIZATION”, “ORGANIZING
    INFLAMMATION”
    WOUND HEALING
    • 1st INTENTION • 2nd INTENTION

    • Edges lined up • Edges NOT lined up


    • Ergo….
    • More granulation
    • More
    epithelialization
    • MORE FIBROSIS
    “HEALTHY” Granulation Tissue
    FIBROSIS/SCARRING
    • DEPOSITION OF COLLAGEN by
    FIBROBLASTS
    • With time (weeks, months,
    years?) the collagen becomes
    more dense, ergo, the tissue
    becomes “STRONGER”
    Wound RETARDING factors
    (LOCAL)
    • DECREASED Blood supply
    • Denervation
    • Local Infection
    • FB
    • Hematoma
    • Mechanical stress
    • Necrotic tissue
    Wound RETARDING factors
    (SYSTEMIC)
    • DECREASED Blood supply
    • Age
    • Anemia
    • Malignancy
    • Malnutrition
    • Obesity
    • Infection
    • Organ failure

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